Process for producing 4-aminopyrimidines



Patented Feb. 6, 1951 PROCESS FOR PRODUCING 4-AMINO- PYRHVIIDINES Arthur W. Larchar, Mendenhall, Pa., assignor to E. I. du Pont de Nemours & Company, Wilmington, DeL, a corporation of Delaware No Drawing. Application July 10, 1948,

Serial No. 38,161

a This invention relates to a novel method for preparing aminopyrimidines.

The preparation of i-aminopyrimidines by heating a nitrile in the presence of alkaline condensing agents has been described by numerous investigators. Without exception, these prior workersuhave used large amounts of the condensing-agent, frequently in an amount molecularly equivalent to the nitrile used, i. e., one mole of condensing agent for each mole of nitrile. Thus, the recommended procedure for preparing 4-amfino-2,6-climethylpyrimidine, as described by Ronaio and Cook, Organic Syntheses, 24, 6 (1944), involves the use of 70 grams of potassium methoxigle condensing agent and 41 grams of acetonitrile. The methods of the prior art, employing 'iarge quantities of alkaline condensing agents, have given yields of the order of 35 to 65 per cent but in no case greater than 70 per cent. This invention has as an object the preparation of--4-a1ninopyrimidines. A further object is the provision of an improved process for the preparation of this class of compounds. Another object is the obtaining of improved yields of these compounds. A still further object is an economy in the preparation of these compounds. Other objects will appear hereinafter.

These objects are accomplished by the following invention wherein a 4-aminopyrimidine is prepared by heating a nitrile in which the cyano group is attached to a carbon bearing at least two hydrogens at 100-200" C. in the presence oi. but catalytic amounts, i. e., 0.005 to 0.05 mole, per mole of nitrile, of an alkali metal alkoxide.

Thefapplication of the invention to acetonitrile gives 4 -amino-2,6-dimethylpyrimidine according to the equation:

omo ycNH, somoN n N on (9H: 'I'heinvention is illustrated in the following examples wherein, unless otherwise specified,

partsare by weight and degrees are on the centigrade scale. 1

Example I An autoclave was filled to of its capacity with a acetonitrile and four The autoclave was approximately half mixture of 196 parts of parts of sodium methoxide. heated at 150 for twelve 8 Claims. (Cl. 260256.4)

hours, with agitationgby rocking; The crude product, a yellow solid, was codistilled with approximately 1500 parts of kerosene. From the distillate there was separated by filtration 4- amino-2,6-dimethylpyrimidine as a white, crystalline solid melting at 182-183. The conversion was 86% (168 parts of pure product).

That the product formed is 4-amino-2,6-dimethylpyrimidine was established by running a mixed melting point ,with an authentic sample of 4-amino-2,6-dimethylpyrimidine obtained from another source. Themixture melted at 182-183". The melting point of 4-amino-2,6-dimethylpyrimidine, as given by Schmidt, Ber. 35, 1575 (1902), is 183.

The product obtained from a run identical with that further identified as 4-amino-2,6-dimethylpyrimidine' by conversion to the corresponding N- by reaction with acetic anhy- The product, (4-acetamino-2,6-dimethyl- ":Pinner, Ber. 17, 174 (1354) reports a melting point of 185 for this" compound.

r I Example II with agitation by rocking. The crude product From the original filtrate 26 parts nitrile and propionitrile or a mixture of ben'zonitrile and propionitrile. When using a mixture of nitriles only one of the nitriles need contain The preferred nitriles are mononitriles, particularly those of formula RCHzCN wherein 1B is hydrogen or .a saturated hydrocarbon radical, i. e., nitriles having a -CmCN group and being, apart from the CN group, saturated aliphatic hydrocarbon.

The condensing agents used in the process of this invention are alkali alkoxides and any alkali metal alkoxide may be used. The preferred alkoxides are those derived from monohydric alkanols containing up to 5 carbon atoms. Exam ples of suitable agents of this type are sodium, potassium, and lithium methoxides, ethoxides, propoxides, and butoxides. Other alkaline con! densing agents, e. g., potassium hydroxide, ammonia and piperidine, can be used to obtain -aminopyrimidines but require more drastic conditions or give large amounts of by-iproduct. Thus, in the case of acsodamide, sodium hydroxide,

I heating a nitrile etonitrile and ammonia at 150 C. a pressure of g at least 4,000 atmospheres is required to obtain significant conversions to the ieaminopyrimidine.

The main advantages of the process of the present invention over prior processes are that much less condensing agent is used and that purification is simplified since there are fewer by-products....:The yields are also higher. The overall advantage is, therefore, one of economy.

. The 4-aminolpyri-midines obtainable by the process of this invention can be used as intermediates in the-preparation of dyes, bactericides and resins.

The foregoing detailed description has been given for clea-rness of understanding only and no unnecessary limitations are to be understood therefrom. The invention is not limited to the exact detailsshown and described for obvious modifications will occur to those skilled in the art.

Whatis claimed is:

'1'.- In the preparation of -aminopyrimidines by heating a nitrile having a cyano, .-.-CN, group attached to a group with an alkaline condensing agent, the improvement wherein the nitrile is heated with from 0.005 to 0.05 mole, per mole of nitrile, of an alkali metal alkoxide and the 4-aminopyrimidine is recovered.

2. In the preparation ofA-aminopyrimidines by heating a nitrile havinga cyano, -.CN, group attached-to a -CH2-.- group with an alkaline (Ondensing a nt, th mprovement wherein the 4 nitrile is heated with from 0.005 to 0.05 mole, per mole of nitrile, of sodium methoxide and the 4-aminopyrimidine is recovered.

3. In the preparation of 4-amino-2,6-dimethylpyrimidine by heating acetonitrile with an alkaline condensing agent, the improvement wherein the acetonitrile is heated with from 0.005 to 0.05 mole, per mole of acetonitrile, of an alkali metal alkoxide and the 4-amino-2,6-dimethyl pyrimidine is recovered.

4. In the preparation of 4-amino-2,6-dimethyipyrimidine by heating acetonitrile with an alkaline condensing agent, the improvement wherein the acetonitrile is heated with from 0.005 to 0.05 mole,- per mole of acetonitrile, of sodium methoxide and the 4-amino-2,6-dimethylpyrimidine is recovered.

(5. In the preparation of d-aminopyrimidines having a cyano, -CN, group attached to a -CH2- group with an alkaline condensing agent, the improvement wherein the nitrile is heated with about 2% by weight oiaikali metal alkoxide and the er-aminopyrimidine is. recovered. 4

5. In t pr paration or e-aminopyrimidi-nea by heating a nitrile RCHzCN Where RCHz is. an alkyl group with an alkaline condensing agent, the improvement whereinv the nitrile is heated with about 2% by weight of alkali metal alkoxide and the 4-aminopyrimioline is recovered.

'7, In the preparation of 4-amino-2,6-dimethylpyrimidine by heating acetonitrile with an 9.1- kaline condensing agent, the improvement wherein the acetonitrile is heated with about 2% byweight of alkali metal alkoxide and the ami-r no-2,6-dimethylpyrirnidine is. recovered.

,8. In the preparation of 4-amino-2,6-diethyl-v 5-methylpyrimidine by heating propionitrilewithan alkaline condensing agent, the improvement wherein the \propionitrile is heated with from 0.005 to 0.05 mole, per mole of propionitrile, of an alkali metal alkoxide and the 4 -amino-.2 ,6-.diethyi-5-methylpyrimidine is recovered.

ARTHUR W. LARCHAR;

REFERENCES CITED Wache: J. prakt. Chem. 39 245 (1889). Schwarze: J. prakt, Chem. 42 3 (1890).

Herfeldt: J. prakt. Chem. 53 246 (1896). 

1. IN THE PREPARATION OF 4-AMINOPYRIMIDINES BY HEATINGA NITRILE HAVING A CYANO, -CN, GROUP ATTACHED TO A -CH2- GROUP WITH AN ALKALINE CONDENSING AGENT, THE IMPROVEMENT WHEREIN THE NITRILE IS HEATED WITH FROM 0.005 TO 0.05 MOLE, PER MOLE OF NITRILE, OF AN ALKALI METAL ALKOXIDE AND THE 4-AMINOPYRIMIDINE IS RECOVERED. 